Stroke is a cerebrovascular event which occurs when the normal blood flow to the brain is disrupted, and the brain receives too little blood. Approximately 15 million people worldwide suffer a stroke each year.
There are two forms of stroke: ischemic stroke, caused by a blood clot that blocks or prevents the flow of blood, and hemorrhagic stroke, caused by bleeding into the brain. Ischemic stroke is responsible for about one third of all deaths in industrialized countries and is the major cause of serious, long-term disability in adults over the age of 45.
Ischemic stroke results from insufficient cerebral circulation of blood caused by obstruction of the inflow of blood. The most common cause is narrowing of the arteries in the neck or head such as through atherosclerosis. Blood clots may form that can block the artery where they are formed (thrombosis), or can dislodge and become trapped in arteries closer to the brain (embolism). Another cause of stroke is blood clots dislodged from the heart. Blood clots can occur as a result of irregular heartbeat (for example, atrial fibrillation), heart attack, or abnormalities of the heart valves. Additional causes of ischemic stroke include the use of street drugs, traumatic injury to the blood vessels of the neck, or disorders of blood clotting
During acute ischemic stroke, the arterial occlusion results in an infarcted core of brain tissue, where cerebral blood flow is reduced to below 10% to 25%. The infarcted core suffers irreversible damage due to significant cell death. The ischemic penumbra, ischemic but still viable tissue, suffers a delayed and less severe infarct.
Administration of thrombolytic agents, such as tissue plasminogen activator (tPA), which dissolve blood clots and thus restore blood flow to affected regions, have limited applicability. In particular, administration of tPA is only effective if given within three hours from the time of stroke onset. There is therefore an unmet need for other methods for the prevention and treatment of brain damage due to stroke.